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Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis (2023)
Journal Article
Guillen-Guio, B., Paynton, M. L., Allen, R. J., Chin, D. P., Donoghue, L. J., Stockwell, A., …Hollox, E. J. (in press). Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis. ERJ Open Research, 00553-2023. https://doi.org/10.1183/23120541.00553-2023

IntroductionIdiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF and a prior assoc... Read More about Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.

Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity (2023)
Journal Article
Portelli, M. A., Bhaker, S., Pang, V., Bates, D. O., Johnson, S. R., Mazar, A. P., …Sayers, I. (2023). Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity. Clinical and Translational Allergy, 13(10), Article e12293. https://doi.org/10.1002/clt2.12293

AbstractBackgroundExpression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.Objective... Read More about Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity.

Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk (2023)
Journal Article
Shrine, N., Izquierdo, A. G., Chen, J., Packer, R., Hall, R. J., Guyatt, A. L., …Consortium Lead Principal Investigators. (2023). Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Nature Genetics, 55, 1778–1779. https://doi.org/10.1038/s41588-023-01531-7

Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation (2023)
Journal Article
Rajasekar, P., Hall, R. J., Binaya, K., Mahapatra, P. S., Puppala, S. P., Thakker, D., …Clifford, R. L. (2023). Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation. Environmental Pollution, 337, Article 122561. https://doi.org/10.1016/j.envpol.2023.122561

Household air pollution caused by inefficient cooking practices causes 4 million deaths a year worldwide. In Nepal, 86% of the rural population use solid fuels for cooking. Over 25% of premature deaths associated with air pollution are respiratory in... Read More about Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation.

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection (2023)
Journal Article
Packer, R. J., Shrine, N., Hall, R., Melbourne, C. A., Thompson, R., Williams, A. T., …Wain, L. V. (2023). Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection. European Respiratory Journal, 61(6), Article 2201667. https://doi.org/10.1183/13993003.01667-2022

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its cause... Read More about Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk (2023)
Journal Article
Shrine, N., Izquierdo, A. G., Chen, J., Packer, R., Hall, R. J., Guyatt, A. L., …The Qatar Genome Program Research (QGPR) Consortium. (2023). Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Nature Genetics, 55(3), 410-422. https://doi.org/10.1038/s41588-023-01314-0

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020... Read More about Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank (2022)
Journal Article
Fawcett, K. A., Demidov, G., Shrine, N., Paynton, M. L., Ossowski, S., Sayers, I., …Hollox, E. J. (2022). Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank. BMC Medical Genomics, 15, Article 119. https://doi.org/10.1186/s12920-022-01268-y

Background The role of copy number variants (CNVs) in susceptibility to asthma is not well understood. This is, in part, due to the difficulty of accurately measuring CNVs in large enough sample sizes to detect associations. The recent availability... Read More about Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank.

Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease (2022)
Journal Article
Guyatt, A., John, C., Williams, A. T., Shrine, N., Reeve, N. F., Sayers, I., …SpiroMeta consortium. (2023). Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease. Thorax, 78(5), 496-503. https://doi.org/10.1136/thoraxjnl-2021-217993

Rationale Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil c... Read More about Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.

Genetic Associations and Architecture of Asthma-COPD Overlap (2022)
Journal Article
John, C., Guyatt, A. L., Shrine, N., Packer, R., Olafsdottir, T. A., Liu, J., …Tobin, M. D. (2022). Genetic Associations and Architecture of Asthma-COPD Overlap. Chest, 161(5), 1155-1166. https://doi.org/10.1016/j.chest.2021.12.674

Background Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. Research Question What is the genetic architecture of asthma-CO... Read More about Genetic Associations and Architecture of Asthma-COPD Overlap.

Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations (2021)
Journal Article
Portelli, M. A., Rakkar, K., Hu, S., Guo, Y., Adcock, I. M., & Sayers, I. (2021). Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations. Frontiers in Allergy, 2, Article 738741. https://doi.org/10.3389/falgy.2021.738741

Asthma affects more than 300 million people globally and is both under diagnosed and under treated. The most recent and largest genome-wide association study investigating moderate to severe asthma to date was carried out in 2019 and identified 25 in... Read More about Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations.

Genetics of Asthma: Insights From Genome Wide Association Studies (2021)
Book Chapter
Cooper, R. M., Bingham, K., Portelli, M. A., & Sayers, I. (2022). Genetics of Asthma: Insights From Genome Wide Association Studies. In Encyclopedia of Respiratory Medicine (308-325). (Second Edition). Elsevier. https://doi.org/10.1016/B978-0-08-102723-3.00155-4

Asthma is a heterogeneous respiratory disease that can be influenced by genetic and environmental factors leading to disease susceptibility and progression. Genome-wide association studies (GWAS) of asthma have yielded replicated findings and identif... Read More about Genetics of Asthma: Insights From Genome Wide Association Studies.

Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells (2021)
Journal Article
Hall, R. J., O'Loughlin, J., Billington, C. K., Thakker, D., Hall, I. P., & Sayers, I. (2021). Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells. FASEB Journal, 35(7), Article e21300. https://doi.org/10.1096/fj.202002073R

GPR126 is an adhesion G protein-coupled receptor which lies on chromosome 6q24. Genetic variants in this region are reproducibly associated with lung function and COPD in genome wide association studies (GWAS). The aims of this study were to define t... Read More about Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells.

Epithelial cell dysfunction, a major driver of asthma development (2020)
Journal Article
Heijink, I. H., Kuchibhotla, V. N. S., Roffel, M. P., Maes, T., Knight, D. A., Sayers, I., & Nawijn, M. C. (2020). Epithelial cell dysfunction, a major driver of asthma development. Allergy, 75(8), 1902-1917. https://doi.org/10.1111/all.14421

Airway epithelial barrier dysfunction is frequently observed in asthma and may have important implications. The physical barrier function of the airway epithelium is tightly interwoven with its immunomodulatory actions, while abnormal epithelial repa... Read More about Epithelial cell dysfunction, a major driver of asthma development.

Phenotypic and functional translation of IL33 genetics in asthma (2020)
Journal Article
Ketelaar, M. E., Portelli, M. A., Dijk, F. N., Shrine, N., Faiz, A., Vermeulen, C. J., …Nawijn, M. C. (2021). Phenotypic and functional translation of IL33 genetics in asthma. Journal of Allergy and Clinical Immunology, 147(1), 144-157. https://doi.org/10.1016/j.jaci.2020.04.051

© 2020 Background: Asthma is a complex disease with multiple phenotypes that may differ in disease pathobiology and treatment response. IL33 single nucleotide polymorphisms (SNPs) have been reproducibly associated with asthma. IL33 levels are elevate... Read More about Phenotypic and functional translation of IL33 genetics in asthma.

Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium (2020)
Journal Article
Portelli, M. A., Dijk, F. N., Ketelaar, M. E., Shrine, N., Hankinson, J., Bhaker, S., …Sayers, I. (2020). Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium. JCI insight, 5(8), Article 132446. https://doi.org/10.1172/jci.insight.132446

The IL1RL1 (ST2) gene locus is robustly associated with asthma; however, the contribution of single nucleotide polymorphisms (SNPs) in this locus to specific asthma subtypes and the functional mechanisms underlying these associations remain to be def... Read More about Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium.

Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis (2019)
Journal Article
Allen, R. J., Guillen-Guio, B., Oldham, J. M., Ma, S., Dressen, A., Paynton, M. L., …Wain, L. V. (2020). Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine, 201(5), 564-574. https://doi.org/10.1164/rccm.201905-1017oc

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of... Read More about Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis.

Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice (2019)
Journal Article
Liu, B., Henry, A. P., Azimi, S., Miller, S., Lee, F. K., Lee, J. C., …Hall, I. P. (2019). Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice. PLoS ONE, 14(9), Article e0221899. https://doi.org/10.1371/journal.pone.0221899

Introduction: Genome-Wide Association Studies suggest glutathione S transferase C terminal domain (GSTCD) may play a role in development of Chronic Obstructive Pulmonary Disease. We aimed to define the potential role of GSTCD in airway inflammation a... Read More about Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice.

Defining a role for lung function associated gene GSTCD in cell homeostasis (2019)
Journal Article
Henry, A. P., Probert, K., Stewart, C. E., Thakker, D., Bhaker, S., Azimi, S., …Sayers, I. (2019). Defining a role for lung function associated gene GSTCD in cell homeostasis. Respiratory Research, 20(1), Article 172. https://doi.org/10.1186/s12931-019-1146-3

Genome wide association (GWA) studies have reproducibly identified signals on chromosome 4q24 associated with lung function and COPD. GSTCD (Glutathione S-transferase C-terminal domain containing) represents a candidate causal gene in this locus, how... Read More about Defining a role for lung function associated gene GSTCD in cell homeostasis.

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries (2019)
Journal Article
Shrine, N., Guyatt, A. L., Erzurumluoglu, A. M., Jackson, V. E., Hobbs, B. D., Melbourne, C. A., …Wain, L. V. (2019). New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Nature Genetics, 51(3), 481-493. https://doi.org/10.1038/s41588-018-0321-7

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which ar... Read More about New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.

Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study (2018)
Journal Article
Shrine, N., Portelli, M. A., John, C., Soler Artigas, M., Bennett, N., Hall, R., …Sayers, I. (2019). Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study. Lancet Respiratory Medicine, 7(1), 20-34. https://doi.org/10.1016/S2213-2600%2818%2930389-8

Background Few genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribut... Read More about Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study.

Genetic risk factors for the development of pulmonary disease identified by genome-wide association (2018)
Journal Article
Hall, R., Hall, I. P., & Sayers, I. (2018). Genetic risk factors for the development of pulmonary disease identified by genome-wide association. Respirology, 24(3), 204-214. https://doi.org/10.1111/resp.13436

Chronic respiratory diseases are a major cause of morbidity and mortality. Asthma and chronic obstructive pulmonary disease (COPD) combined affect over 500 million people worldwide. While environmental factors are important in disease progression, as... Read More about Genetic risk factors for the development of pulmonary disease identified by genome-wide association.

Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study (2017)
Journal Article
Allen, R. J., Porte, J., Braybrooke, R., Flores, C., Fingerlin, T. E., Oldham, J. M., …Jenkins, R. G. (2017). Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study. Lancet Respiratory Medicine, 5(11), https://doi.org/10.1016/S2213-2600%2817%2930387-9

Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified a significant genetic risk associated with the development of IPF; however,... Read More about Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.

Defining the inflammatory signature of human lung explant tissue in the presence and absence of glucocorticoid (2017)
Journal Article
Rimington, T. L., Hodge, E., Billington, C. K., Bhaker, S., K C, B., Kilty, I., …Sayers, I. (2017). Defining the inflammatory signature of human lung explant tissue in the presence and absence of glucocorticoid. F1000Research, 6, Article 460. https://doi.org/10.12688/f1000research.10961.1

Background: Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help st... Read More about Defining the inflammatory signature of human lung explant tissue in the presence and absence of glucocorticoid.

Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways (2017)
Journal Article
Kheirallah, A. K., de Moor, C. H., Faiz, A., Sayers, I., & Hall, I. P. (2017). Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways. BMC Genomics, 18(1), Article 248. https://doi.org/10.1186/s12864-017-3628-3

BACKGROUND: Genetic studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung... Read More about Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways.

Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets (2017)
Journal Article
Wain, L. V., Shrine, N., Artigas, M. S., Erzurumluoglu, A. M., Noyvert, B., Bossini-Castillo, L., …Hall, I. P. (2017). Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. Nature Genetics, 49(3), 416-425. https://doi.org/10.1038/ng.3787

Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function dist... Read More about Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.

Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls (2017)
Journal Article
Artigas, M. S., Wain, L. V., Shrine, N., McKeever, T. M., Sayers, I., Hall, I. P., & Tobin, M. D. (2017). Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls. PLoS ONE, 12(1), Article e0170222. https://doi.org/10.1371/journal.pone.0170222

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function meas... Read More about Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls.

Genome-wide association studies in asthma (2016)
Journal Article
Portelli, M. A., & Sayers, I. (in press). Genome-wide association studies in asthma. https://doi.org/10.1002/9780470015902.a0024639

Asthma is a complex respiratory disease, with both genetic and environmental factors contributing to disease susceptibility. Genome-wide association studies (GWAS) have now identified novel risk alleles and loci associated with asthma diagnosis and m... Read More about Genome-wide association studies in asthma.

The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro (2016)
Journal Article
Miller, S., Henry, A. P., Hodge, E., Kheirallah, A. K., Billington, C. K., Rimington, T. L., …Sayers, I. (2016). The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro. PLoS ONE, 11(10), Article e0164041. https://doi.org/10.1371/journal.pone.0164041

Introduction Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Recepto... Read More about The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro.

Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identi?es a severe, nonatopic subset of patients (2016)
Journal Article
Portelli, M. A., Moseley, C., Stewart, C. E., Postma, D. S., Howarth, P., Warner, J., …Sayers, I. (in press). Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients. Allergy, https://doi.org/10.1111/all.13046

Rationale: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studieshave identi?ed uPAR... Read More about Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identi?es a severe, nonatopic subset of patients.

The differential effects of azithromycin on the airway epithelium in vitro and in vivo (2016)
Journal Article
Slater, M., Torr, E., Harrison, T. W., Forrester, D. L., Knox, A., Shaw, D. E., & Sayers, I. (2016). The differential effects of azithromycin on the airway epithelium in vitro and in vivo. Physiological Reports, 4(18), 1-15. https://doi.org/10.14814/phy2.12960

Macrolides including azithromycin (AZM) can improve clinical symptoms in asthma regardless of infection status. The mechanisms underlying these benefi- cial effects are yet to be elucidated. The aim of this study was to determine the effect of AZM on... Read More about The differential effects of azithromycin on the airway epithelium in vitro and in vivo.

Expression of polycomb protein BMI-1 1 maintains the plasticity of basal 2 bronchial epithelial cells (2016)
Journal Article
Torr, E., Heath, M., Mee, M., Shaw, D. E., Sharp, T. V., & Sayers, I. (2016). Expression of polycomb protein BMI-1 1 maintains the plasticity of basal 2 bronchial epithelial cells. Physiological Reports, 4(16), 1-14. https://doi.org/10.14814/phy2.12847

The airway epithelium is altered in respiratory disease and is thought to contribute to disease aetiology. A caveat to disease research is that the technique of isolation of bronchial epithelial cells from patients is invasive and cells have a limite... Read More about Expression of polycomb protein BMI-1 1 maintains the plasticity of basal 2 bronchial epithelial cells.

Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development (2016)
Journal Article
Miller, S., Melén, E., Merid, S. K., Hall, I. P., & Sayers, I. (in press). Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development. Respiratory Research, 17(95), https://doi.org/10.1186/s12931-016-0410-z

Background Recent meta-analyses of genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within/near 54 genes associated with lung function measures. Current understanding of the contribution of these genes to human... Read More about Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development.

Traditional and emerging indicators of cardiovascular risk in chronic obstructive pulmonary disease (2016)
Journal Article
John, M., McKeever, T. M., Haddad, M. A., Hall, I. P., Sayers, I., Cockcroft, J. R., & Bolton, C. E. (2016). Traditional and emerging indicators of cardiovascular risk in chronic obstructive pulmonary disease. Chronic Respiratory Disease, 13(3), https://doi.org/10.1177/1479972316636995

With the increased cardiovascular (CV) morbidity and mortality in subjects with chronic obstructive pulmonary disease (COPD), there is a priority to identify those patients at increased risk of cardiovascular disease. Stable patients with COPD (n = 1... Read More about Traditional and emerging indicators of cardiovascular risk in chronic obstructive pulmonary disease.

Translating lung function genome-wide association study (GWAS) findings: new insights for lung biology (2016)
Journal Article
Kheirallah, A. K., Miller, S., Hall, I. P., & Sayers, I. (2016). Translating lung function genome-wide association study (GWAS) findings: new insights for lung biology. Current Advances in Genetics and Molecular Biology, 93, https://doi.org/10.1016/bs.adgen.2015.12.002

Chronic respiratory diseases are a major cause of worldwide mortality and morbidity. Although hereditary severe deficiency of ?1 antitrypsin (A1AD) has been established to cause emphysema, A1AD accounts for only ?1% of Chronic Obstructive Pulmonary D... Read More about Translating lung function genome-wide association study (GWAS) findings: new insights for lung biology.

The challenge of measuring IL-33 in serum using commercial ELISA: lessons from asthma (2016)
Journal Article
Ketelaar, M. E., Nawijn, M. C., Shaw, D. E., Koppelman, G. H., & Sayers, I. (2016). The challenge of measuring IL-33 in serum using commercial ELISA: lessons from asthma. Clinical and Experimental Allergy, 46(6), 884-887. https://doi.org/10.1111/cea.12718

Background Interleukin-33 (IL-33) has been subject of extensive study in the context of inflammatory disorders, particularly in asthma. Many human biological samples, including serum, have been used to determine the protein levels of IL-33, aiming t... Read More about The challenge of measuring IL-33 in serum using commercial ELISA: lessons from asthma.

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12 (2016)
Journal Article
Jackson, V. E., Ntalla, I., Sayers, I., Morris, R., Whincup, P., Casas, J., …Wain, L. V. (in press). Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12. Thorax, 71(6), https://doi.org/10.1136/thoraxjnl-2015-207876

Background Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants. Objective To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated... Read More about Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12.

Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation (2015)
Journal Article
Artigas, M. S., Wain, L. V., Miller, S., Kheirallah, A. K., Huffman, J. E., Ntalla, I., …Tobin, M. D. (2015). Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation. Nature Communications, 6, 1-12. https://doi.org/10.1038/ncomms9658

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC... Read More about Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

Response (2015)
Journal Article
Sayers, I., Portelli, M. A., & Siedlinski, M. (2015). Response. FASEB Journal, 29(12), https://doi.org/10.1096/fj.15-1201LTER

We thank Dr. Rasmussen and colleagues for their comments on our work outlined in “Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels” (FASEB J. 28, 923–934) and the opportunity to... Read More about Response.

Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank (2015)
Journal Article
Wain, L. V., Shrine, N., Miller, S., Jackson, V. E., Ntalla, I., Artigas, M. S., …Hall, I. P. (2015). Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank. Lancet Respiratory Medicine, 3(10), https://doi.org/10.1016/S2213-2600%2815%2900283-0

Background Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behav... Read More about Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank.

Pharmacogenetics of Asthma (2015)
Book Chapter
Fenech, A. G., Sayers, I., & Portelli, M. A. (2015). Pharmacogenetics of Asthma. In G. Grech, & I. Grossman (Eds.), Preventive and Predictive Genetics: Towards Personalised Medicine (241-274). Cham: Springer. https://doi.org/10.1007/978-3-319-15344-5_9

The study of pharmacogenetics has expanded from what were initially casual drug response observations present in families, to a fully-fledged science with direct therapeutic applications, within a timespan of less than 60 years. Within the field of a... Read More about Pharmacogenetics of Asthma.

Genetic risk factors for the development of allergic disease identified by genome-wide association (2015)
Journal Article
Portelli, M. A., Hodge, E., & Sayers, I. (2015). Genetic risk factors for the development of allergic disease identified by genome-wide association. Clinical and Experimental Allergy, 45(1), https://doi.org/10.1111/cea.12327

An increasing proportion of the worldwide population is affected by allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and allergic asthma and improved treatment options are needed particularly for severe, refractory disease. Al... Read More about Genetic risk factors for the development of allergic disease identified by genome-wide association.

Cigarette smoke and the induction of urokinase plasminogen activator receptor in vivo: selective contribution of isoforms to bronchial epithelial phenotype (2014)
Journal Article
Portelli, M. A., Stewart, C. E., Hall, I. P., Brightling, C. E., & Sayers, I. (2015). Cigarette smoke and the induction of urokinase plasminogen activator receptor in vivo: selective contribution of isoforms to bronchial epithelial phenotype. American Journal of Respiratory Cell and Molecular Biology, 53(2), 174-183. doi:10.1165/rcmb.2014-0296oc

The urokinase plasminogen activator receptor (uPAR) gene (PLAUR) has been identified as an asthma susceptibility gene, with polymorphisms within that gene being associated with baseline lung function, lung function decline, and lung function in a smo... Read More about Cigarette smoke and the induction of urokinase plasminogen activator receptor in vivo: selective contribution of isoforms to bronchial epithelial phenotype.

Mouse Protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo (2014)
Journal Article
Koning, H., Oosterhout, A. J. V., Brouwer, U., Boef, L. E. D., Gras, R., Reinders-Luinge, M., …Nawijn, M. C. (2014). Mouse Protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo. PLoS ONE, 9(7), Article e98197. https://doi.org/10.1371/journal.pone.0098197

Protocadherin-1 (PCDH1) is a novel susceptibility gene for airway hyperresponsiveness, first identified in families exposed to cigarette smoke and is expressed in bronchial epithelial cells. Here, we asked how mouse Pcdh1 expression is regulated in l... Read More about Mouse Protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.

The impact of azithromycin therapy on the airway microbiota in asthma (2014)
Journal Article
Slater, M., Rivett, D. W., Williams, L., Martin, M., Harrison, T. W., Sayers, I., …Shaw, D. E. (2014). The impact of azithromycin therapy on the airway microbiota in asthma. Thorax, 69(7), https://doi.org/10.1136/thoraxjnl-2013-204517

There is interest in the use of macrolide antibiotics in asthma. Macrolides have been shown to improve airway hyperresponsiveness (AHR) and measures of airway inflammation.The degree of AHR may relate to the microbiota present in the airways, with a... Read More about The impact of azithromycin therapy on the airway microbiota in asthma.

Genome-wide association analysis identifies six new loci associated with forced vital capacity (2014)
Journal Article
Loth, D. W., Artigas, M. S., Gharib, S. A., Wain, L. V., Franceschini, N., Koch, B., …London, S. J. (2014). Genome-wide association analysis identifies six new loci associated with forced vital capacity. Nature Genetics, 46(7), 669-677. https://doi.org/10.1038/ng.3011

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies an... Read More about Genome-wide association analysis identifies six new loci associated with forced vital capacity.

Clonally expanded human airway smooth muscle cells exhibit morphological and functional heterogeneity (2014)
Journal Article
Singh, S. R., Billington, C. K., Sayers, I., & Hall, I. P. (2014). Clonally expanded human airway smooth muscle cells exhibit morphological and functional heterogeneity. Respiratory Research, 15(1), Article 57. https://doi.org/10.1186/1465-9921-15-57

Background: Mesenchyme-derived airway cell populations including airway smooth muscle (ASM) cells, fibroblasts and myofibroblasts play key roles in the pathogenesis of airway inflammation and remodeling. Phenotypic and functional characterisation of... Read More about Clonally expanded human airway smooth muscle cells exhibit morphological and functional heterogeneity.

Whole Exome Re-Sequencing Implicates CCDC38 and Cilia Structure and Function in Resistance to Smoking Related Airflow Obstruction (2014)
Journal Article
Wain, L. V., Sayers, I., Soler Artigas, M., Portelli, M. A., Zeggini, E., Obeidat, M., …Tobin, M. D. (2014). Whole Exome Re-Sequencing Implicates CCDC38 and Cilia Structure and Function in Resistance to Smoking Related Airflow Obstruction. PLoS Genetics, 10(5), Article e1004314. https://doi.org/10.1371/journal.pgen.1004314

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with l... Read More about Whole Exome Re-Sequencing Implicates CCDC38 and Cilia Structure and Function in Resistance to Smoking Related Airflow Obstruction.

Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma (2014)
Journal Article
Wain, L. V., Odenthal-Hesse, L., Abujaber, R., Sayers, I., Beardsmore, C., Gaillard, E. A., …Hollox, E. J. (2014). Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma. PLoS ONE, 9(1), Article e84192. https://doi.org/10.1371/journal.pone.0084192

Lung function measures are heritable, predict mortality and are relevant in diagnosis of chronic obstructive pulmonary disease (COPD). COPD and asthma are diseases of the airways with major public health impacts and each have a heritable component. G... Read More about Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma.

Identification of a novel regulatory mechanism for the disease associated protein, uPAR (2014)
Journal Article
Portelli, M. A., Hall, I. P., & Sayers, I. (2014). Identification of a novel regulatory mechanism for the disease associated protein, uPAR. Malta Medical Journal, 26(1), 32-37

Expression quantitative trait loci (eQTLs), as determined through a series of statistical association studies collectively known as genome-wide association (GWA) studies, have provided us with a hypothesis free approach for the investigation into reg... Read More about Identification of a novel regulatory mechanism for the disease associated protein, uPAR.

Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels (2013)
Journal Article
Portelli, M., Siedlinski, M., Stewart, C. E., Postma, D. S., Nieuwenhuis, M. A., Vonk, J. M., …Sayers, I. (2013). Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels. FASEB Journal, 28(2), https://doi.org/10.1096/fj.13-240879

The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated... Read More about Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels.

Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children (2013)
Journal Article
Tulah, A. S., Holloway, J. W., & Sayers, I. (2013). Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children. BMC Medical Genetics, 14(100), https://doi.org/10.1186/1471-2350-14-100

Background: Asthma genome-wide association studies (GWAS) have identified several asthma susceptibility genes with confidence; however the relative contribution of these genetic variants or single nucleotide polymorphisms (SNPs) to clinical endpoints... Read More about Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children.

GSTCD and INTS12 regulation and expression in the human lung (2013)
Journal Article
Obeidat, M., Miller, S., Probert, K., Billington, C. K., Henry, A. P., Hodge, E., …Hall, I. P. (2013). GSTCD and INTS12 regulation and expression in the human lung. PLoS ONE, 8(9), Article e74630. https://doi.org/10.1371/journal.pone.0074630

Genome-Wide Association Study (GWAS) meta-analyses have identified a strong association signal for lung function, which maps to a region on 4q24 containing two oppositely transcribed genes: glutathione S-transferase, C-terminal domain containing (GST... Read More about GSTCD and INTS12 regulation and expression in the human lung.

HTR4 gene structure and altered expression in the developing lung (2013)
Journal Article
Hodge, E., Nelson, C. P., Miller, S., Billington, C. K., Stewart, C. E., Swan, C., …Sayers, I. (2013). HTR4 gene structure and altered expression in the developing lung. Respiratory Research, 14(77), https://doi.org/10.1186/1465-9921-14-77

Background: Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT4R) gene (HTR4) associated with lung function. The aims of this study were t... Read More about HTR4 gene structure and altered expression in the developing lung.

Leukotriene B4 receptor locus gene characterisation and association studies in asthma (2012)
Journal Article
Tulah, A. S., Beghé, B., Barton, S. J., Holloway, J. W., & Sayers, I. (2012). Leukotriene B4 receptor locus gene characterisation and association studies in asthma. BMC Medical Genetics, 13(Novemb), Article 11. https://doi.org/10.1186/1471-2350-13-110

Background: Polymorphisms spanning genes involved in the production of leukotriene B4 (LTB4) e.g. ALOX5AP and LTA4H are associated with asthma susceptibility, suggesting a role for LTB4 in disease. The contribution of LTB4 receptor polymorphism is... Read More about Leukotriene B4 receptor locus gene characterisation and association studies in asthma.

Genome-wide association study to identify genetic determinants of severe asthma (2012)
Journal Article
Wan, Y., Shrine, N., Soler Artigas, M., Wain, L., Blakey, J., Moffatt, M., …Hall, I. P. (2012). Genome-wide association study to identify genetic determinants of severe asthma. Thorax, 67(9), https://doi.org/10.1136/thoraxjnl-2011-201262

Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify co... Read More about Genome-wide association study to identify genetic determinants of severe asthma.

Genetic basis for personalized medicine in asthma (2012)
Journal Article
Portelli, M. A., & Sayers, I. (2012). Genetic basis for personalized medicine in asthma. Expert Review of Respiratory Medicine, 6(2), https://doi.org/10.1586/ers.12.9

There is heterogeneity in patient responses to current asthma medications. Significant progress has been made identifying genetic polymorphisms that influence the efficacy and potential for adverse effects to asthma drugs, including; ?2-adrenergic re... Read More about Genetic basis for personalized medicine in asthma.